Although phylogenetic analysis shows coronaviruses (CoV) share similar genome sequences, CoVs encode different number of proteins (5 to 14), which has implication on viral pathogenicity and infection. Here, we aimed to identify (in-silico) the similarities between different members of coronavirus family. The analysis included 50 coronavirus proteomes, including SARS-CoV-2 (COVID-19), to find the variation of the number of protein functional motifs and domain in each coronavirus. For this role, we used the experimentally validated domain (motif) that known to be crucial for viral infection. Although human CoVs are classified within one genus, we found variations among them. SARS-CoV-1, SARS-CoV-2 and MERS-CoV encode different type of domains, which has implications on the molecular interactions triggered by each virus within human cells. Secondly, we used functional motifs to reconstruct the potential molecular pathways or interactions triggered by SARS-CoV-2 proteins within human cell.

Neuronal lesion or injury is a traditional approach to investigate neural circuit. Is any new neural pathway or new neurodegeneration related central nerve system injury? Spinal disc herniation can cause the spinal cord injury. However, the histological examination is still lack. It happened that a case of spinal disc herniation of a 10-year old dog was examined with NADPH diaphorase (N-d) histology. We did not find the N-d neurodegenerative aberrant in the tissue of the mid-rostral lumber segment besides the metamorphoses by the compression of the disc herniation. However, the severe neuropathological changes majorly occurred in the lumbosacral spinal cord. We found more diverse neurodegenerative alterations: the aging-related N-d body (ANB), megaloneurite and N-d homogeneous formazan globule in the lumbosacral spinal cord. We also found that a new circuit pathway (intermedial collateral pathway) showed by a megaloneurite between the lateral collateral pathway and the medial collateral pathway. The enormous notch caused by spinal disc herniation located at the mid-rostral lumber segments. The aging-related neurodegeneration occurred the specific lumbosacral segments. The homogeneous formazan globule was round or oval homogeneous N-d positivity which distributed in the gray matter and dorsal column. In the medulla oblongata, ANBs were revealed in the gracile nucleus, nucleus reticularis lateralis (ventrolateral spinal trigeminal nucleus) and middle of the spinal trigeminal nucleus.

The COVID-19-medical emergency has ended worldwide, yet there is still a need to evaluate the psychological impact of these years of unprecedented changes on students’ life. Methods: This study aims to assess and compare COVID-19-related stressors (Relationships-and-Academic-Life; Isolation; Fear-of-Contagion) and psychophysical symptoms reported by university students in April-2020, April 2021, and April 2022. The predictive role of COVID-19-related stressors on psychophysical symptoms within each time was also tested. Data were collected among 637 university students in April-2020 (n = 197), April-2021 (n = 200), April-2022 (n = 240). Results: In April-2022, perceived Isolation and Fear-of-Contagion decreased from the peak registered in April-2021, but stress related to Relationships-and-Academic-Life remained noteworthy high. A sharp and ongoing increase in psychophysical symptoms was found, with more than 50% of students reporting clinical levels of Sleep-Disorders, Depression, Psychoticism, and Interpersonal-Sensitivity. In April-2022, students still perceiving stress related to Relationships-and-Academic-Life and Isolation were at risk for Anxiety, Somatization, and Sleep-Disorders, while those still perceiving stress related to Fear-of-Contagion were also at risk for Depression, Obsessive-Compulsive, and Psychoticism. Conclusion: Findings emphasized the long-lasting detrimental effects of the COVID-19-related stress. Interventions must pinpoint the complex post-pandemic adjustment process and their effects on university students' psychophysical health.

Assessment of health-related quality of life (HRQoL) after pediatric traumatic brain injury (TBI) has been limited in children and adolescents due to a lack of disease-specific instruments. To fill this gap, the Quality of Life after Traumatic Brain Injury for Children and Adolescents (QOLIBRI-KID/ADO) was developed for the German-speaking population. Reference values from a comparable general population are essential for comprehending the impact of TBI on health and well-being. This study examines the validity of the German QOLIBRI-KID/ADO in a general pediatric population in Germany and provides reference values for use in clinical practice. Overall, 1997 children and adolescents aged 8-17 years from the general population and 300 from the TBI population participated in the study. The questionnaire was tested for reliability and validity. A measurement invariance (MI) approach was used to assess the comparability of the HRQoL construct between both samples. Reference values were determined by percentile-based stratification according to factors that significantly influenced HRQoL in regression analyses. The QOLIBRI-KID/ADO demonstrated strong psychometric properties. The HRQoL construct was measured largely equivalently in both samples, and reference values could be provided. The QOLIBRI-KID/ADO was considered reliable and valid for assessing HRQoL in a general German-speaking pediatric population, allowing for clinically meaningful comparisons between general and TBI populations.

Pachychoroid neovasculopathy (PNV) is a pachychoroid-spectrum disease. As blood circulation throughout the choroid may be involved in PNV pathogenesis, analysis using ultra-wide-field (UWF) fundus imaging is crucial. We evaluated choroidal thickness after half-fluence photodynamic therapy (PDT) combined with intravitreal aflibercept injection for PNV using UWF swept-source optical coherence tomography. Seventeen eyes with PNV that underwent half-fluence PDT with adjuvant single intravitreal aflibercept injection were analyzed. To compare choroidal thicknesses in the central and peripheral choroids, we set subfields <3, <9, and 9–18 mm from the fovea. The <9- and 9–18-mm subfields were divided into four quadrants. Choroidal thickness in each subfield decreased significantly after half-fluence PDT (P<0.001); this reduction was more pronounced in the central area. We also investigated the relationship between the dominant side of the deep choroidal veins that harbor choroidal vein efflux from the macula. When choroidal thickness in the supratemporal and infratemporal 9x9-mm subfields were evaluated, the ratio of choroidal thickness reduction was not significantly different between the dominant and non-dominant sides. The dominant side was not associated with the extent of choroidal thickness reduction in PNV. In conclusion, half-fluence PDT caused thinning of the entire choroid, especially in the central area, in PNV.

: Healthcare workers are affected by mental health issues, burnout and turnover, and this burden is even greater during epidemics and pandemics, such as COVID-19. The purpose of this research is to provide an overview of the measures introduced or supported in the institutions of Quebec’s health and social services network during the COVID-19 pandemic with the aim of protecting healthcare workers’ mental health. An online questionnaire survey was administered in 2021 among human resources department personnel in health and social services network institutions involved in workplace mental health in Quebec. A total of 223 key informants representing 31 of the 34 public health and social services institutions in the province of Quebec in Canada responded to the questionnaire. Measures that focus on the needs of staff, involve all levels of authority and the ones that provide flexibility, support and recognition at work were more successful, according to the advisors surveyed. Future research into whether the same measures are considered effective or ineffective outside of a pandemic context is needed.

In recent years, the interaction between adiponectin (APN), a versatile fat-associated adipokines, and eye disorders has become a captivating focus of interest. Unveiling the intricate relationship between APN and its receptors (AdipoRs) with aging eye disorders has emerged as a fascinating frontier in medical research. This review article delves into this captivating connection, illuminating the hidden influence of adipocytokine, APN on retinal health. This comprehensive review critically examines the latest findings and breakthroughs that underscore the pivotal roles of APN/AdipoRs signaling in maintaining ocular homeostasis and protecting against eye ailments. Here, we meticulously explore the intriguing mechanisms by which APN protein influences retinal function, lens clarity, and overall visual acuity. Drawing from an extensive array of cutting-edge studies, the article highlights APN's multifaceted functions, ranging from anti-inflammatory properties and oxidative stress reduction to angiogenic regulation within retinal and macula tissues. The involvement of APN/AdipoRs in mediating these effects opens up novel avenues for potential therapeutic interventions targeting prevalent aging eye conditions. Moreover, this review unravels the interplay between APN signaling pathways and age-related macular degeneration (AMD). The single-cell RNA seq results validate the expression of both the receptor isoform (AdipoR1/R2) in retinal cells. The transcriptomic analysis showed lower expression of AdipoR1/2 in dry AMD pathogenesis compared to healthy subjects. The inhibitory peptide (APN1) demonstrated over 75% suppression of CNV, whereas the control peptide did not exert any inhibitory effect on CNV. The elucidation of these relationships fosters a deeper under-standing of adipose tissue's profound influence on ocular health, presenting new prospects for personalized treatments and preventative measures. In conclusion, "Obesity Hormone's Role in Aging Eyes: Linking Adiponectin/AdipoRs to AMD" provides a captivating journey into the enthralling world of APN intertwining the realms of adipose biology and aged ophthalmology.

Age-related macular degeneration (AMD) causes visual impairment in individuals >50 years of age. However, no study has investigated AMD using ultra-wide-field swept-source optical co-herence tomography (UWF SS-OCT). We aimed to evaluate central and peripheral choroidal thickness using UWF SS-OCT and compare AMD subtypes. We included 75 eyes of patients with typical AMD (tAMD), 56 with polypoidal choroidal vasculopathy (PCV), 29 with pachychoroid neovasculopathy (PNV), and 12 with retinal angiomatous proliferation (RAP). To compare cho-roidal thicknesses in the central and peripheral choroids, we established subfields of <3 mm, <9 mm, and 9–18 mm from the fovea. PNV patients were significantly younger than those with tAMD (P=0.01). The choroidal thicknesses of PNV were significantly greater than that of tAMD in all subfields (P<0.01) and choroidal thickness significantly correlated with age and axial length in all subfields (P<0.05). Even after adjusting for age and axial length, the choroidal thickness in PNV was significantly greater than that in tAMD (P<0.05). In addition, the ratio of the posterior < 9 mm to peripheral 9–18 mm choroidal thickness in PNV was significantly greater than that in tAMD (P<0.01). A thickened choroid in PNV was more pronounced in the posterior choroid than in the periphery.

Tightly regulated and robust mitochondrial activities are critical for normal hearing. Previously, we demonstrated that Fus1 KO mice with mitochondrial dysfunction exhibit premature hearing loss. Molecular analysis of the cochlea revealed hyperactivation of the mTOR pathway, oxidative stress, altered mitochondrial morphology and quantity, suggesting compromised energy sensing and production. Here, we investigated whether pharmacological modulation of metabolic pathways using rapamycin (RAPA) or 2-deoxy-D-glucose (2-DG) supplementation can protect against hearing loss in female Fus1 KO mice. Additionally, we aimed to identify mitochondria- and Fus1-dependent molecular pathways and processes critical for hearing. We found that inhibiting mTOR or activating alternative mitochondrial energetic pathways to glycolysis protected hearing in the mice. Comparative gene expression analysis revealed dysregulation of critical biological processes in the KO cochlea, including mitochondrial metabolism, neural and immune responses, and cochlear hypothalamic–pituitary–adrenal axis signaling system. RAPA and 2-DG mostly normalized these processes, although some genes showed a drug-specific response or no response at all. Interestingly, both drugs resulted in a pronounced upregulation of critical hearing-related genes not altered in the non-treated KO cochlea, including cytoskeletal and motor proteins, and Ca2+-linked transporters and voltage-gated channels. These findings suggest that pharmacological modulation of mitochondrial metabolism and bioenergetics may restore and activate processes critical for hearing, thereby protecting against hearing loss

Background: The link between nocturia and aging male symptoms (AMS) has not been scientifically established. This study aimed to measure the degree of severity of AMS that impact on the health-related quality-of-life (HRQoL) in adult males living with nocturia, and to determine the predictive values of nocturnal factors on AMS. Methods: It is an extended analysis of new data collected by using the Hong Kong Traditional AMS (HK-AMS) scale and Cantonese version of the Pittsburgh Sleep Quality Index (PSQI) in a recently published cross-sectional population-based survey. Results: Of the 781 respondents that have completed the set of questionnaires, 68% and 61% of men living with nocturia reported clinically significant (at moderate-to-severe levels) somato-vegetative and sexual AMS, whereas the prevalence and severity were increased with advancing nighttime voiding frequency. The nocturia-specific QoL (NQoL) score and nocturnal frequency were found to be significant predictive factors for composite, somato-vegetative and sexual AMS, in addition to age, global OSQI score, and certain metabolic diseases. Conclusions: Current findings suggested the inclusion of nocturia when measuring the male-specific HRQoL related to aging.

Persistent Spinal Pain Syndrome Type 2 (PSPS-T2), (Failed Back Surgery Syndrome), dramatically impacts on patient quality of life, as evidenced by Health-Related Quality of Life (HRQoL) assessment tools. However, the importance of functioning, pain perception and psychological status in HRQoL can substantially vary between subjects. Our goal was to extract patient profiles based on HRQoL dimensions in a sample of PSPS-T2 patients and to identify factors associated with these profiles. Two classes were clearly identified using a mixture of mixed effect models from a clinical data set of 200 patients enrolled in “PREDIBACK”, a multicenter observational prospective study including PSPS-T2 patients with 1-year follow-up. We observed that HRQoL was more impacted by functional disability for first class patients (n=136) and by pain perception for second class patients (n=62). Males that perceive their work as physical were more impacted by disability than pain intensity. Lower education level, lack of adaptive coping strategies and higher pain intensity were significantly associated with HRQoL being more impacted by pain perception. The identification of such classes allows for a better understanding of HRQoL dimensions and opens the gate towards optimized health-related quality of life evaluation and personalized pain management.

Background. Wnt-pathway proteins play a vital role in kidney development and defects in the Wnt-pathway are associated with kidney disorders. However, the knowledge on the role of Wnt/β-catenin pathway proteins in end-stage renal disease (ESRD) is limited.Aim of the study. To delineate the association of ESRD and Wnt-proteins including the agonistR-spondin 1, the transducer β-catenin and the antagonists Dickkopf-related protein 1 (DKK1) and sclerostin.Methods. Serum Wnt-pathway proteins levels were measured by ELISA, while other biochemicals were measured spectrophotometrically in 60 ESRD patients and 30 normal controls.Results. DKK1 and sclerostin were significantly higher in ESRD than in controls, and β-catenin and the catenin + R-Sponin-1 / DKK1 + sclerostin ratio, reflecting the ratio of agonist and transducer on antagonists (AT/ANTA), were significantly lower in ESRD. Logistic regression analysis showed that ESRD was significantly predicted by increased levels of DDK1 and sclerostin and lowered β-catenin (p<0.001). eGFR was significantly associated with DKK1 and sclerostin (inversely), β-catenin (positively) and the AT/ANTA ratio (r=0.468, p<0.001). DKK1 levels were significantly and positively correlated with urea, creatinine, and copper. DKK1 and sclerostin were inversely associated with hemoglobin and packet cell volume. Catenin was significantly negatively associated with copper, urea and creatinine.Conclusion. Wnt/β-catenin pathway proteins show significant alterations in ESRD, indicating significantly increased levels of antagonists and, therefore, attenuated Wnt/β-catenin pathway activity. The latter is associated with lowered eGFR and increased serum copper levels. Wnt/β-catenin pathway proteins are possible drug targets to treat ESRD or its consequences.

Late January 2020, COVID-19 unexpectedly imposed world-wide limitations on daily life. Deemed a pandemic mid-March 2020, lockdowns were imposed for an indefinite period, including at academic institutions. Consequently, interest in digital literacy—an on-going and increasing concern of academic institutions in the 21^st century—exponentially heightened. Continuing meetings of academic groups now necessitated online communication. In the almost overnight closure of all non-essential services, academic units at one post-secondary institution expeditiously selected Zoom—a popular video conferencing application—as the preferred platform for meetings until social distancing was lifted. In contrast to this widely accepted use of Zoom for scheduled meetings, one unique health-related group at the institution, tailored to the 4Cs of 21^st century learning of critical thought, communication, cooperation and creativity, found social networking through a private Facebook group a more appropriate and satisfying group experience than likely possible with the Zoom app. Pros and cons of both online platforms are presented along with when each choice is warranted. In promoting digital literacy as the primary goal in online communication for academic meetings, private Facebook groups hold promise for collaborative online academic meetings with similar features to this health-related group.

C-reactive protein (CRP) and leukocytes are blood biomarkers involved in "Inflamm-Aging", which is a risk factor for the onset and progression of age-related diseases. Studies show that higher serum concentrations of these biomarkers are associated with functional disability, increased risk of low muscle strength, decreased muscle mass and mortality in the elderly. The objective was to estimate the predictive power and discriminating criteria of C-reactive protein and leukocyte concentrations for the risk of adverse health factors in the elderly within 30 days after hospital discharge (HD). Prospective cohort study using exploratory methods and blood biomarkers with 135 older adults admitted to medical and surgical clinics at a government hospital. The elderly were monitored at home after 30 days of HD for adverse health factors (rehospitalization, falls, amount of medication consumed, disability in basic and instrumental activities of daily living and mortality). CRP> 2.4; ≥ 0.7 and> 24.7 mg / dL and leukocytes ≥ 6.410; ≥ 8.690 and> 8.310 mm³ were discriminant for rehospitalization, falls and mortality within 30 days after HD, respectively. The cut-off points described may be used as a reference in the screening of hospitalized elderly vulnerable to adverse health events after hospital discharge.

The present review focuses on recent clinical trials that analyze the efficacy of intravitreal therapeutic agents for the treatment of dry age-related macular degeneration (AMD), such as neuroprotective drugs, and complement inhibitors, also called immunomodulatory or anti-inflammatory. A systematic literature search was performed to identify randomized controlled trials published prior to January 2019. Patients affected by dry AMD treated with intravitreal therapeutic agents were included. The changes in the correct visual acuity and the reduction in geographic atrophy progression were evaluated. Several new drugs have shown some promising results, including those targeting the complement cascade and agents called neuroprotective. The action potential of the two groups of drugs is to block the complement cascade model for immunomodulating agents, and prevent the degeneration and apoptosis of ganglion cells for the neuroprotectors, respectively. To the best of knowledge, and after extensive studies on the matter, there are still many investigations to be carried out on dry AMD in collaboration between researchers. They will have to identify truly effective molecules, understand the practical potential of pluripotent stem cells, and refine gene therapies. Only in-depth clinical trials will be able to allow the most appropriate and personalized treatments for each dry AMD patient.

Background: Mental capacity is a fundamental aspect that enables patients to fully par-ticipate in various healthcare procedures. To assist healthcare professionals (HCPs) in assessing patients' capacity, especially in the mental health field, several standardized tools have been developed. These tools include the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), the MacArthur Competence Assessment Tool for Clinical Research (MacCAT-CR), and the Competence Assessment Tool for Psychiatric Advance Directives (CAT-PAD). The core dimensions explored by these tools include Understanding, Appreciation, Reasoning, and Expression of a choice. Objective: This meta-analysis aimed to investigate potential differences in deci-sion-making capacity within the healthcare context among groups of patients with bi-polar disorder (BD) and schizophrenia spectrum disorder (SSD). Methods: A systematic search was conducted on Medline/Pubmed, and Scopus. Addi-tionally, Google Scholar was manually inspected, and a manual search of emerging re-views and reference lists of the retrieved papers was performed. Eligible studies were specifically cross-sectional, utilizing standardized assessment tools, and involving pa-tients diagnosed with BD and SSD. Data from the studies were independently extracted and pooled using random-effect models. Hedges g was used as a measure for outcomes. Results: Six studies were identified, with three studies using the MacCAT-CR, two studies the MacCAT-T, and one the CAT-PAD. The participants included 189 individuals with BD and 324 individuals with SSD. The meta-analysis revealed that patients with BD performed slightly better, and the difference was statistically significant, compared to patients with SSD, particularly in the domain of Appreciation (ES=0.23, 95% CI: 0.01 to 0.04, p=0.037). There was no statistically significant difference between the two groups for Understanding (ES=0.09, 95% CI: - 0.10 to 0.27, p=0.352), Reasoning (ES=0.18, 95% CI: - 0.12 to 0.47, p=0.074), and Expression of a choice (ES = 0.23, 95% CI: - 0.01 to 0.48, p=0.60). In the sensitivity analysis, furthermore, when considering only studies involving patients in symptomatic remission, the difference for Appreciation also resulted in non-significant (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). (ES=0.21, 95% CI: -0.04 to 0.46, p=0.102). Conclusions: These findings indicate that there are no significant differences between patients with BD and SSD during remission phases, while differences are minimal during acute phases. The usefulness of standardized assessment of capacity at any stage of the illness should be considered, both for diagnostic-therapeutic phases and for research and advance directives. Further studies are necessary to understand the reasons for the overlap in capacity between the two diagnostic categories compared in this study.

Background: we aim to investigate attitudes toward vaccination, by analyzing empirical factors associated with vaccine acceptance in the Lazio region mpox vaccination (MpoxVax) campaign in Italy. Methods: all subjects who accessed to MpoxVax and signed the informed consent were prospectively enrolled in the MPOX-VAC Study and were asked to fill out an anonymous survey. Two endpoints were selected: ‘delayed acceptance’ and ‘early acceptance’, defined as access for vaccination &gt;60 and ≤30 days from the vaccination campaign starting (VCS), respectively. Results: over the study period 1717 individuals underwent vaccination: 129 (7%) &gt;60 [1588 (92.5%) ≤60] and 676 (60%) ≤30 days from VCS. A bisexual orientation, a lower education level and a worse perceived physical and mental health were associated with delayed access to vaccination. Being Pre-Exposure Prophylaxis (PrEP) users and, marginally, HIV positive, having a high perceived risk for mpox infection and reporting high-risk behaviors like the use of recreational drugs/chems, sex under the influence of drugs and/or alcohol and higher number of principal sexual partners, were associated with early access to vaccination. Conclusions: according to our data, risk awareness was a major determinant of early mpox vaccination acceptance. Conversely, worse perceived health status and a low educational level were critical factors associated with delayed vaccination.

Zn is an essential element for children related to optimal growth, development and nutritional metabolism. We measured Zn bioaccesibility (Zn-BA) levels of foods by Inductively coupled plasma mass spectrometry (ICP-MS) after in vitro digestion-fermentation method from children with gluten related disorders (GRD-CH), obesity (OB-CH) and allergy/intolerance to cow’s milk proteins (AICM-CH). Zn-BA levels in sick children (34.7 ± 28.8, 29.6 ± 30.1 and 26.7 ± 30.4%, respectively) were significantly lower (p &lt; 0.05) than in healthy norm-weight children (HE-CH). For AICM-CH, Zn-BA in animal foods was significantly lower than in plant foods, and in both plant and animal foods from sick and healthy children (p &lt; 0.05). In foods of animal origin in sick and healthy children, Zn-BA in foods heated in liquid media (frying and boiling) was significantly higher than in foods heated by hot air (roasting and grilling). In conclusion, in children the studied diseases diminished the Zn-BA, probably by the alteration of the gut microbiota which could negatively affect their appropriate long-term development. In AICM-CH, the allergy to cow's milk proteins could induce intestinal dysbiosis and inflammatory processes, leading to allergies to other animal food proteins, and to a more pronounced decrease of Zn-BA.

Spherical harmonic (SH) interpolation is a commonly used method to spatially up-sample sparse Head Related Transfer Function (HRTF) datasets to denser HRTF datasets. However, depending on the number of sparse HRTF measurements and SH order, this process can introduce distortions in high frequency representation of the HRTFs. This paper investigates whether it is possible to restore some of the distorted high frequency HRTF components using machine learning algorithms. A combination of Convolutional Auto-Encoder (CAE) and Denoising Auto-Encoder (DAE) models is proposed to restore the high frequency distortion in SH interpolated HRTFs. Results are evaluated using both Perceptual Spectral Difference (PSD) and localisation prediction models, both of which demonstrate significant improvement after the restoration process.

Background: The mortality and severity in COVID-19 is increased in patients with comorbidities. The aim of this study was to evaluate the unknown risk of severity and mortality in COVID-19 patients with underlying kidney and liver diseases. Method: We retrieved data on the clinical features and primary composite end point of COVID-19 patients released from inception till 16^th of April 2020 from Medline and Embase. The data on two comorbidities, liver diseases and chronic kidney disease, present in COVID-19 were pooled and statistically analysed to explain the associated severity and mortality rate. Results: 142 abstracts were screened, and 41 full articles were then read. In total, 22 studies including 5595 COVID-19 patients were included in this study with case fatality rate of 16%. The prevalence of liver diseases and CKD were 3% (95%CI; 2%-3%) and 1% (95%CI; 1%-2%) respectively. In patients with COVID-19 and underlying liver diseases, 57.33% (43/75) cases were severe with 17.65% mortality. While in CKD patients with COVID-19, 83.93% (47/56) severity and 53.33% (8/15) mortality were reported. Conclusion: This study found an increased risk of severity and mortality in COVID-19 patients with liver diseases and CKD. This will allow for better clinical management and inform more stringent preventative measures for this group of patients.

Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged >=65 years in developed countries. Globally, it affects 30-50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form. Many observational studies, such as AREDS-1 and AREDS 2, have shown a potential role of micronutrient supplementation in lowering the risk of progression of the early stages of AMD. Recently, low-grade inflammation, sustained by dysbiosis and a leaky gut, has been shown to contribute to the development of AMD. Given the ascertained influence of the gut microbiota in systemic low-grade inflammation and its potential modulation by macro- and micro-nutrients, a potential role of diet in AMD has been proposed. This review discusses the role of the gut microbiota in the development of AMD. Using PubMed, Web of Science and Scopus, we searched for recent scientific evidence discussing the impact of dietary habits (high fat and high glucose or fructose diets), micronutrients (vitamins C, E, and D, zinc, beta-carotene, lutein and zeaxanthin) and omega-3 fatty acids on the modulation of the gut microbiota and their relationship with AMD risk and progression.

This study addresses the influence of working conditions on Work-Related Quality of Life (WRQOL) among Spanish healthcare professionals. The research seeks to elucidate the mediating roles of job engagement and burnout, and the moderating effects of resilience and self-efficacy, in this relationship. Methods: The study included 374 healthcare workers from Spain, encompassing physicians, nurses, and nursing assistants. It employed a methodological approach using validated instruments to assess psychosocial risks, work-life quality, job engagement, burnout, and resilience. Data were gathered through self-reported questionnaires. Results: Key findings indicate a negative association between working conditions and WRQOL. Job engagement and burnout significantly mediated this relationship, accounting for 19% to 33% of the variance in WRQOL. Notably, lack of support emerged as a strong negative factor for work-related quality of life. Additionally, resilience moderated the relationship between lack of support and burnout. Conclusions: The study concludes that improving working conditions could increase WRQOL. Interventions aimed at enhancing engagement and addressing burnout may be effective. The moderating role of resilience suggests that strategies to enhance resilience could also be beneficial. These findings hold significant implications for policy formulation and human resources planning in healthcare, emphasizing the need for enhanced workplace support and the development of resilience among health workers.

Age-related macular degeneration (AMD) is a leading cause of blindness worldwide. In late-stage AMD, geographic atrophy (GA) of dry AMD or choroidal neovascularization (CNV) of neovascular AMD results in macular atrophy (MA), leading to significant visual loss. Despite the development of innovative therapies, there are currently no established effective treatments for MA. As a result, early detection of MA is critical in identifying later central macular involvement throughout time. Accurate and early diagnosis is achieved through a combination of clinical examination and imaging techniques. Our review of the literature depicted advances in retinal imaging to identify biomarkers of progression and risk factors for late AMD. Imaging methods like fundus autofluorescence (FAF), near-infrared reflectance (NIR), widefield imaging, optical coherence tomography (OCT), multicolor confocal scanning laser ophthalmoscopy (cSLO), and optical coherence tomography angiography (OCTA) can be used to detect and monitor the progression of retinal atrophy. Multifocal electroretinogram (ERG) and microperimetry are methods for quantifying visual function to map disease progression. The evolving diverse imaging modalities optimize detection of pathology anatomy and measurement of visual function; they may also contribute to the understanding of the underlying mechanistic pathways, particularly the underlying MA changes in late AMD.

We previously showed that mice with knockout in the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) gene encoding the PGC-1a protein and nuclear factor erythroid 2 like 2 (NFE2L2) gene, showed some features of the age-related macular degeneration (AMD) phenotype. To further explore the mechanism behind the involvement of PGC-1a in AMD pathogenesis we used young (3-month) and old (12-month) mice with knockout in the PPARGC1A gene and age-matched wild-type (WT) animals. An immunohistochemical analysis showed age-dependent different expression of markers of oxidative stress defense, senescence and autophagy in the retinal pigment epithelium of KO animals as compared with their WT counterparts. Multivariate inference testing showed that senescence and autophagy proteins had the greatest impact on the discrimination between KO and WT 3-month animals, but proteins of antioxidant defense also contributed to that discrimination. A bioinformatic analysis showed that PGC-1a might coordinate the interplay between genes encoding proteins involved in antioxidant defense, senescence and autophagy in the aging retina. These data support importance of PGC-1a in AMD pathogenesis and confirm the utility of mice with PGC-1a knockout as an animal model to study AMD pathogenesis.

After three years of the onset of the pandemic, there is scarce evidence about how COVID-19 disease affect the female reproductive system, and consequently, the menstrual cycle. Since the common causes of secondary amenorrhea are considered as exclusion criteria in the studies about menstrual changes following SARS-CoV-2 infection, the prevalence of this event and the influencing factors in formerly menstruating women remains unknown. A retrospective observational cross-sectional study was conducted on Spanish adult women (N= 17,512), using an online survey; a subpopulation of SARS-CoV-2-infected-formerly menstruating women was included in the present analysis (n= 72). Collected data included general characteristics, medical history, and specific information about COVID-19 disease. 38.9% of the respondents experienced menstrual-related disturbances after suffering from the COVID-19 disease, unexpected vaginal bleeding being the most common (20.8%). Other alterations related with the length – “shorter” by 12.5% − and the flow − “heavier than usual” 30.3% − of the menstrual bleeding were reported. The binary logistic regression showed that being a perimenopausal woman (AOR 4.608, CI 95%, 1.018 – 20.856, p = 0.047) and having heavy menstrual bleeding (AOR 4.857, CI 95%, 1.239 – 19.031, p=0.023) are influential factors. This evidence could help health professionals to provide scientifically up-to-date information to their patients, empowering them to actively manage their reproductive health, especially in those societies where menstrual health is still a taboo.

Oxidative stress (OS) is involved in the pathogenesis of retinal neurodegenerative diseases like age-related macular degeneration (AMD) and diabetic retinopathy (DR) and an important target of therapeutic treatments. New therapeutics are tested in vivo despite limits in transferability and ethical concerns. Retina cultures using human tissue can deliver critical information and significantly reduce the number of animal experiments along with increased transferability. We cultured up to 32 retina samples derived from one eye, analyzed models’ quality, induced OS, and tested efficiency of antioxidative therapeutics. Bovine, porcine, rat, and human retinae were cultured in different experimental settings for 3-14 d. OS was induced by high-glucose or hydrogen peroxide (H2O2) and treated by Scutellarin, pigment epithelium-derived factor (PEDF), and/or granulocyte macrophage-colony stimulating factor (GM-CSF). Tissue morphology, cell viability, inflammation, and glutathione level were determined. Retina samples showed only moderate necrosis (23.83±5.05 increased to 27.00±1.66 AU PI-staining over 14 d) after 14 days in culture. OS was successfully induced (reduced ATP content of 288.3±59.9 vs. 435.7±166.8 nM ATP in controls); antioxidants reduced OS-induced apoptosis (from 124.20±51.09 to 60.80±319.66 cells/image after scutellarin-treatment). Enhanced mammalian animal and human retina cultures allow reliable, highly transferable research on OS-triggered age-related diseases and pre-clinical testing during drug development.

Work-related thoughts in off-job time have been studied extensively in occupational health psychology and related fields. We provide a focused review of research on overcommitment – a component within the effort-reward imbalance model – and aim to connect this line of research to the most commonly studied aspects of work-related rumination. Drawing on this integrative review, we analyze survey data on ten facets of work-related rumination, namely (1) overcommitment, (2) psychological detachment, (3) affective rumination, (4) problem-solving pondering, (5) positive work reflection, (6) negative work reflection, (7) distraction, (8) cognitive irritation, (9) emotional irritation, and (10) inability to recover. First, we leverage exploratory factor analysis to self-report survey data from 357 employees to calibrate overcommitment items and to position overcommitment within the nomological net of work-related rumination constructs. Second, we leverage confirmatory factor analysis to self-report survey data from 388 employees to provide a more specific test of uniqueness vs. overlap among these constructs. Third, we apply relative weight analysis to quantify the unique criterion-related validity of each work-related rumination facet regarding (1) physical fatigue, (2) cognitive fatigue, (3) emotional fatigue, (4) burnout, (5) psychosomatic complaints, and (6) satisfaction with life. Our results suggest that several measures of work-related rumination (e.g., overcommitment and cognitive irritation) can be used interchangeably. Emotional irritation and affective rumination emerge as the strongest unique predictors of fatigue, burnout, psychosomatic complaints, and satisfaction with life. Our study assists researchers in making informed decisions on selecting scales for their research and paves the way for integrating research on effort-reward imbalance and work-related rumination.

Fear extinction requires coordinated neural activity within the amygdala and medial prefrontal cortex (mPFC). Any behavior has a transcriptomic signature that is modified by environmental experiences, and specific genes are involved in functional plasticity and synaptic wiring during fear extinction. Here, we investigated the effects of optogenetic manipulations of prelimbic (PrL) pyramidal neurons on amygdala gene expression to analyze the specific transcriptional pathways involved in adaptive and maladaptive fear extinction. To this aim, transgenic mice were (or not) fear-conditioned and during the extinction phase they received optogenetic (or sham) stimulations over PrL pyramidal neurons. At the end of behavioral testing, electrophysiological (neural cellular excitability and Excitatory Post-Synaptic Currents) and morphological (spinogenesis) correlates were evaluated in the PrL pyramidal neurons. Furthermore, transcriptomic cell-specific RNA-analyses (differential gene expression profiling and functional enrichment analyses) were performed in amygdala pyramidal neurons. Our results show that the optogenetic activation of PrL pyramidal neurons in fear-conditioned mice induces fear extinction deficits, reflected in an increase of cellular excitability, excitatory neurotransmission, and spinogenesis of PrL pyramidal neurons, and in strong modifications of the transcriptome of amygdala pyramidal neurons. Understanding the electrophysiological, morphological and transcriptomic architecture of fear extinction may facilitate the comprehension of fear-related disorders.

Objective: Diabetes is associated with increased cardiovascular and cerebrovascular disease-related mortality. We investigated the association between carotid intima-media thickness (CIMT) with clusterin (CLU), amylin, secreted frizzled-related protein-4 (SFRP-4), total and active glucagon-like peptide-1 (GLP-1) levels, and dipeptidyl peptidase-4 (DPP-4) in type 2 diabetes mellitus (T2DM) individuals with or without coronary artery disease (CAD). Methods: This study consisted of four groups in Medicine Hospital between April- October, 2017: Control group (mean ages: 50.3 ± 10.7 years, 20 females and 15 males), diabetic group (DM) (mean ages: 53.9 ± 11.1, 14 females and 23 males), CAD group (mean ages: 62.6 ± 11.8, 17 females and 17 males) and CAD+ DM group: (mean ages: 62.6 ± 11.8 years, 18 females and 18 males). Results: Both CAD and CAD+DM groups have higher CIMT levels than controls. CAD+DM group have also significantly higher CIMT levels than DM group. Left external carotid artery (ECA) was only found different in DM group from controls. When compared with controls, DM, CAD groups have low DPP-4 and GLP-1_total concentration. Control group have significantly lower SFRP-4 levels than DM, CAD and CAD+DM (p<0.001) groups. Serum GLP-1_total levels were found to be significantly low in CAD+DM group when compared to control group. Conclusion: DPP-4 and SFRP-4 levels are predictive marker for atherosclerosis in diabetes, correlates well with HOMA-IR particularly in diabetes. CIMT has the potential to be a clinically useful predictor of vascular risk in diabetic patients with CAD. Large cohorts and at-risk populations are needed to confirm the predictive value of these findings.

Escherichia coli is an indicator microorganism in One Health antibiotic resistance surveillance programmes. The purpose of the study was to describe and compare E. coli isolates obtained from pigs and human contacts from a commercial farm in South Africa using conventional methods and whole genome sequencing (WGS). Porcine E. coli isolates were proportionally more resistant phenotypically and harboured a richer diversity of antibiotic resistance genes, as compared to human E. coli isolates. Different pathovars, namely ExPEC (12.43%, 21/169), ETEC (4.14%; 7/169), EPEC (2.96%, 5/169), EAEC (2.96%, 5/169) and STEC (1.18%, 2/169) were detected at low frequencies. Sequence type complex (STc) 10 were the most prevalent (85.51%, 59/169) among human and porcine isolates. Six STcs (STc10, STc86, STc168, STc206, STc278 and STc469) were shared at the human-livestock interface according to multilocus sequence typing (MLST). Core genome MLST and hierarchical clustering (HC) showed that human and porcine isolates were overall genetically diverse, but some clustering at HC2 to HC200 were observed. In conclusion, even though the isolates shared a spatio-temporal relationship, there were still differences in the virulence potential, antibiotic resistance profiles, and cgMLST and HC according to the source of isolation.

Healthcare workers' stress, burnout, and job dissatisfaction were exacerbated by the Covid-19 pandemic, whose mid-term negative effects are still present. The aim of this study was to investigate in healthcare workers the effect of the dimensions of burnout (Psychophysical exhaustion, Relational deterioration, and Professional inefficacy) on Career satisfaction. These relationships were evaluated by considering the direct and mediated effects of Disillusion. For these purposes, the Link Burnout Questionnaire (LBQ) and the Career Satisfaction Scale (Occupational Stress Indicator - OSI) were administered to 295 healthcare professionals working at three Italian public hospitals in Cagliari, Italy. The analyses were conducted using the Partial Least Square Structural Equation Model (PLS-SEM) method. Findings highlight that healthcare workers were in a condition of work distress, high risk of burnout, and career dissatisfaction. Also recognized was the direct negative effect of burnout dimensions on career satisfaction. Finally, the mediated negative effect of Disillusion in the relationship between burnout and career satisfaction was identified. This study emphasizes the relevance of the dimension of Disillusion, and its “bright side” Fulfilment, in healthcare workers, specifically referring to the disregarded relationship between burnout and career satisfaction.

Number of studies claim that tobacco control (TC) regulations are associated with reductions in smoking-related hospitalisation rates, however very few have estimated the impact of TC laws (TCL) at both countrywide and regional levels, and none of them - in relation to compliance with TC regulations. This study evaluates the effects of Russian TCL on hospital admission (HA) rates for pneumonia countrywide and in 10 Russian regions and the extent of these effects in connection with the compliance to TCL. Methods: HA rates for pneumonia during 2005–2019 were analysed to compare the periods before and after the adoption of TCL in 2013. An interrupted time series design and a Poisson regression model were used to estimate the immediate and long-term effects of TCL on pneumonia annual hospitalisation rates after the TCL adoption, compared with the pre-law period. The 10 Russian regions were compared using the TCL Implementation Scale (TCIS) developed on the basis of the results of Russian TC policy evaluation survey; Spearman’s rank correlation and linear regression models were employed. Results showed a 14.3% reduction in HA rates for pneumonia (RR 0.88; p=0.01) after the adoption of TCL in Russia with significant long-term effect after 2013 (RR 0.86; p=0.006). Regions with better enforcement of TCL exhibited greater reductions in pneumonia HA rates (rsp=−0.55; p=0.04); (=−4.21; p=0.02). Conclusions: TCL resulted in a sustained reduction in pneumonia hospitalisation rates, but these effects, varying by region, may depend on the scale of the TCL enforcement.

Both SARS-CoV-2 (COVID-19) and SARS coronaviruses (CoVs) are members of the subgenus Sarbecovirus. To understand the origin of SARS-CoV-2, protein sequences from sarbecoviruses were analyzed to identify highly-specific molecular markers consisting of conserved inserts or deletions (termed CSIs) in the spike (S) and nucleocapsid (N) proteins that are specific for either particular clusters/lineages of these viruses or are commonly shared by specific lineages. Three novel CSIs in the N-terminal domain of the spike protein S1-subunit (S1-NTD) are uniquely shared by the SARS-CoV-2, BatCoV-RaTG13 and most pangolin CoVs, distinguishing this cluster of viruses (SARS-CoV-2r) from all others. In the same positions, where these CSIs are found, related CSIs are also present in two other sarbecoviruses (viz. CoVZXC21 and CoVZC45 forming CoVZC cluster), which form an out group of the SARS-CoV-2r cluster. These three CSIs are not found in the SARS-CoVs. However, both SARS and SARS-CoV-2r CoVs contain two large CSIs in the C-terminal domain of S1 (S1-CTD), which binds the human ACE-2 receptor, that are absent in the CoVZC cluster of CoVs. These results indicate that while the S1-NTD of the SARS-CoV-2r viruses possesses the sequence characteristics of the CoVZC cluster of CoVs, their S1-CTD resembles the SARS viruses. Thus, the spike protein of SARS-CoV-2r viruses has likely originated from a recombination event between the S1-NTD of the CoVZC viruses and the S1-CTD of SARS viruses. This inference is also supported by the amino acid sequence similarity of the S1-NTD and S1-CTD from SARS-CoV-2 compared to the CoVZC and SARS CoVs. We also present evidence that one of the pangolin-CoV_MP789, whose receptor-binding domain is most similar to the SARS-CoV-2, is also derived by a recent recombination between the S1-NTD of the CoVZC CoVs and the S1-CTD of a SARS-CoV-2 related virus. Several other identified CSIs are specific for others clusters of sarbecoviruses including a clade consisting of bat SARS-CoVs (BM48-31/BGR/2008 and SARS_BtKY72). Structural mappings studies show that the identified CSIs are located within surface-exposed loops and form distinct patches on the surface of the spike protein. These surface loops/patches are predicted to interact with other host components and play important role in the biology/pathology of SARS-CoV-2 virus. Lastly, the CSIs specific for the SARS-CoV-2r clade provide novel means for development of new diagnostic and therapeutic targets for these viruses.

Multiple myeloma (MM) accounts for about 10 to 15% of all diagnosed hematologic malignancies and about 1-2% of all cancer cases. Approximately 80-90% of MM patients develop bone disease and the changes rarely regress. It is only possible to stop or slow their progression. A major role in bone destruction in MM is attributed to the Wnt signaling pathway, and its action can be modified by various types of interventions including training and diet. Therefore, the aim of this project was to evaluate the effects of a Nordic Walking (NW) training cycle and intermittent fasting (IF) on the levels of selected bone turnover markers associated with the Wnt pathway in patients with MM. Results from 35 patients divided into training (NW and IF NW) and non-training (IF and control) groups were included in the analysis. A 6-week training cycle involving 60-minute workouts 3 times a week was conducted. Body mass and composition and the levels of: vitamin D, calcium and phosphorus, beta2-microglobulin and albumin were examined before and after completion of training cycle. Markers of bone turnover were also determined: sclerostin (SOST), Dickkopf-related protein 1 (DKK-1), osteoprotegrin (OPG), osteopontin (OPN) and Tartrate-resistant acid phos-phatase 5b (TRACP 5b). There was no negative effect of IF or combined training and fasting on the nutritional status of the patients (the level of albumines was unchanged). Both training groups showed an increase in serum concentrations of the active metabolite of vitamin D (IF NW and NW: p=0.001 and p=0.022, re-spectively). The change in the concentration of this vitamin negatively correlated with the con-centration of TRACP 5b (r=-0.413, p=0.014). Evaluating the concentrations of markers related to bone turnover, a reduction in the concentrations of SOST (time: p=0.026, time vs. group: p=0.033) and TRACP 5b (time: p

Humans are often exposed to various environmental contaminants, among which phthalates are prevalent due to their extensive use as plasticizers in various consumer goods. Di(2-ethylhexyl) phthalate (DEHP), a widely used phthalate, is recognized as an endocrine disruptor chemical (EDC). DEHP is reported to affect various organs. Few studies have addressed the effects of phthalates on bone. However, the effects of DEHP on the bone forming cells (osteoblasts) are obscure. The present study was peformed to determine the cytotoxic effects of DEHP on human osteoblasts in vitro and to delineate the mechansims. In this study, we exposed the human osteo-blastic cell line MG-63 to various concentrations of DEHP (1, 25, 50 and 100 µM) for 24, 48 and 72 h. Cell viability was assessed by MTT assay. Total RNA and protein were collected after 48 h treatment with 1 and 100 µM DEHP and determined for the mRNA and/or protein expression of alkaline phosphatase (ALP), sex steroid receptors (androgen and estrogen receptors), receptor activator of nuclear factor kappa-Β ligand (RANKL), runt-related transcription factor 2 (RUNX2) and peroxisome proliferator-activated receptor alpha (PPARα). The mRNA expression was stud-ied by real-time RT-PCR analysis and the protein expression was determined by western blot analysis. Statistical analyses were done by one-way analysis of variance (ANOVA) followed by the Students–Newman–Keuls (SNK) test. The exposure of MG-63 cells to DEHP caused a signifi-cant decrease in osteoblast viability in all the treatment groups and at all the time points stud-ied. Interestingly, DEHP exposure decreased the mRNA expression of ALP, a bone formation marker. DEHP had differential effects on estrogen receptor alpha (ERα) mRNA and protein ex-pression. However, DEHP treatment downregulated the mRNA and protein expression of ERβ, and androgen receptor (AR). Surprisingly, DEHP downregulated the RANKL mRNA expression. DEHP decreased the protein expression of RUNX2, the key transcription factor and master regu-lator of bone formation. Furthermore, DEHP increased the PPARα protein expression in the os-teoblasts. Importantly, DEHP increased the reactive oxygen species (ROS) molecules and thus oxidative stress in osteoblasts, as observed by increased hydrogen peroxide, hydroxyl radical levels and lipid peroxidation. On the other hand, it decreased the enzymatic and non-enzymatic antioxidant levels namely catalase, superoxide dismutase, glutathione peroxidase activity and reduced glutathione. Our study demonstrated that in vitro exposure to DEHP reduces the osteo-blast viability possibly through alterations in the oxidant-antioxidant system and modulation of the key genes involved in bone formation, highlighting the cytotoxic effects of DEHP on bone forming cells.

Migraine is a neurovascular disorder that can be debilitating for individuals and society. Current research focuses on finding effective analgesics and management strategies for migraines by targeting specific receptors and neuropeptides. Nevertheless, the responder rates of recently approved calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and receptor inhibitors remain around 50 percent. To address the need for novel therapeutic targets, researchers are exploring the potential of another secretin family peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), as a ground-breaking treatment avenue for migraine. Preclinical models have revealed how PACAP affects the trigeminal system, which is implicated in headache disorders. Clinical studies have demonstrated the significance of PACAP in migraine pathophysiology; however, a few clinical trials remain inconclusive: the pituitary adenylate cyclase-activating peptide 1 receptor mAb, AMG 301 showed no benefit for migraine prevention, while the PACAP ligand mAb, Lu AG09222 significantly reduced the number of monthly migraine days over placebo in a phase 2 clinical trial. Meanwhile, another secretin family peptide vasoactive intestinal peptide (VIP) is gaining interest as a potential new target. In light of recent advances in PACAP research, we emphasize the potential of PACAP as a promising target for migraine treatment, highlighting the significance of exploring PACAP as a member of the antimigraine armamentarium, especially for patients who do not respond to or contraindicated to anti-CGRP therapies. By updating our knowledge on PACAP and its unique contribution to migraine pathophysiology, we can pave the way for reinforcing PACAP and other secretin peptides, including VIP, as a novel treatment option for migraines.

Age-related macular degeneration is one of the most common causes of blindness, and the incidence exhibits profound racial bias, occurring most frequently in Caucasians. A primary cell type affected in the disease is the retinal pigment epithelium, but the etiology is unclear. The end 10% of the photoreceptor outer segments are shed each day, and the underlying retinal pigment epithelium engulfs, digests, and recycles molecules back to the sensory retina. In previous work, we showed that GPR143 signaling in response to L-DOPA may be effective in the prevention or delay of age-related macular degeneration. In this study, we explore a novel potential effector of GPR143 signaling, that of outer segment uptake and digestion. Using isolated outer segments, labelled with a pH-sensitive marker to fluoresce in lysosomes, we show that GPR143 signaling does not impact outer segment uptake, but does have a significant effect on subsequent degradation. Interestingly, GPR143 signaling did not affect the digestive capacity of the cells, marked by total proteolytic capacity and cathepsin D activity. Rather, our data suggest GPR143 improved endosomal trafficking efficiency of the phagocytosed outer segments to the lysosome. This result is similar to the effect we previously reported for GPR143 on exosome release from the endosomal compartment. Our data illustrate that GPR143 is active in endosomal traffic A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article’s main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

Urbanization induced land use land cover (LULC) changes intensify the urban heat island effects. It magnifies the risk of urban dwellers and sometimes causes the loss of human life, defined as heat-related health risk (HRHR). Hence, urban LULC planning plays a crucial role. Present study analyses the impact of composition and configuration of urban LULC defined as urban landscape metric (ULM) on HRHR in Delhi at the ward level. Firstly, the HRHR is measured by using satellite thermal and other digital data. Then, measured HRHR is validated by conducting a rapid field survey. Thirdly, ULM measured at ward level using Fragstat 4 software. Finally, both, HRHR and ULM linked with bi-variate Moran's I and impacts of ULM are assessed using ordinary least square (OLS) and spatial error (SE) regression. The result indicates the high risk is found as clustered in north-east, central and middle of south-west Delhi. Built-up density intensifies HRHR and abundance of vegetation reduce it; however, it is not similar for all vegetation patches. Larger vegetation patches surrounded by dense built-up might not able to reduce the risk as much as a large vegetation patch could in other regions. Findings can be helpful for heat resilient city planning.

Despite extensive use of intravitreal anti-vascular endothelial growth factor (anti-VEGF) biologics for over a decade, neovascular age-related macular degeneration (nAMD) or choroidal neovascularization (CNV) continues to be a major cause of irreversible vision loss in developed countries. Many nAMD patients demonstrate persistent disease activity or experience declined responses over time despite anti-VEGF treatment. The underlying mechanisms of anti-VEGF resistance are poorly understood, and no effective treatment strategies are available to date. Here we review evidence from animal models and clinical studies that supports the roles of neovascular remodeling and arteriolar CNV formation in anti-VEGF resistance. Cholesterol dysregulation, inflammation, and ensuing macrophage activation are critically involved in arteriolar CNV formation and anti-VEGF resistance. Combination therapy by neutralizing VEGF and enhancing cholesterol removal from macrophages is a promising strategy to combat anti-VEGF resistance in CNV.

This study investigated the impact of seven-strain probiotic supplementation on the frequency of T helper 17 (Th17) cells, regulatory T (T-reg) cells, Treg/Th17 ratio, and their gene expression in individuals with severe traumatic brain injury (STBI). Probiotics can influence the gut microbiota, modulate the immune response, and prevent or alleviate certain immune diseases. However, it is necessary to clarify whether probiotics can effectively impact Th cells in STBI patient. Despite the great attention to improving the immune system in most diseases, there is currently no accurate mechanism for the use of probiotics in diseases with damage to the head injury, which can be a basis for the use of probiotics. The primary objective of this study is to address this research gap. The present study was a randomized, double-blind, placebo-controlled trial that enrolled 48 STBI patients. They were treated with probiotics or placebo: 4 capsule/day for 14 days. The pre- and post-study evaluation included examining the frequency of Treg, Th17 cells, as well as the expression of associated immunological parameters (Foxp3 and RORγt) and Treg/Th17 ratio in both groups. No significant differences were found between the two groups in terms of subject characteristics (P>0.05). GCS scores at 14 days were significantly higher in the probiotic compared to the placebo group. The probiotic group showed a significant decrease in Th17 cell and RORγt gene expression (P = 0.022 and P< 0.001, respectively), a notable increase in T-reg and FoxP3 gene expression (P= 0.025 and P< 0.001, respectively), and a higher Treg/Th17 ratio compared to the placebo group. Our study provides promising evidence of the beneficial effects of seven-strain probiotic supplementation on Th cells in individuals with STBI.

High dietary phosphate intake and poor adherence to phosphate-binding-therapy elevate the risk of hyperphosphatemia in maintenance hemodialysis (HD; MHD) patients. Therefore, chronic kidney disease-related mineral and bone disorder (CKD-MBD) indicators increase; consequently, risks of CKD-MBDs and inflammation are elevated. This double-blind, randomized control trial intervention study was designed to investigate the possibility of reducing blood CKD-MBD indicators and modulating inflammatory indicators by consuming low-phosphate (LP) meals accompanied by a minimum dose of a calcium-based phosphate binder (CaCO3). MHD patients were recruited and randomly assigned to an LP meal group (LP group) or a control group. After initial data collection, blood collection, and dietary counseling, subjects were asked to consume a washout diet for 1 week. During the washout diet period, subjects consumed their usual diet but took 1 tablet of calcium carbonate (1CaCO3) as a phosphate binder with each meal. After the washout diet period, subjects in the LP group and control group respectively consumed LP meals and regular meals twice a day for 1 week. Meat in the LP meals was boiled before the regular cooking process, but meat in control meals was not. All meals were supplied by a central kitchen so that the contents of phosphate and other nutrients could be identified. In total, 40 MHD patients completed the study program. After 1 week of the dietary intervention, the blood Ca x P product and dietary phosphate had significantly decreased in the LP group compared to the control group (p&lt;0.05). The LP group had significantly lower variations in dietary phosphate intake, blood calcium, Ca x P product, and tumor necrosis factor (TNF)-α than the control group by comparing differences between after the dietary intervention and the baseline (△after intervention - baseline, p&lt;0.05). The increase in dietary phosphate intake (△3rd - 2nd dietary phosphate intake) augmented the increase in the TNF-α level by 6.24-fold (odds ratio [95% confidence interval]: 6.24 [1.12~34.92], p&lt;0.05). These results highlighted the conclusion that LP meals accompanied by a minimum dose of CaCO3 downregulated pro-inflammation by reducing CKD-MBD indicators which was triggered by decreasing dietary phosphate intake.

To this day, use of oily eye drops and non-invasive retinal delivery remains a major challenge. Oily eye drops usually cause ocular irritation and interfere with normal function of the eye, while ocular injections for retinal drug delivery cause significant adverse effects and a high burden on the healthcare system. Here the authors report a novel topical Non-Invasive Ocular Delivery Platform (NIODP) through the periorbital skin for high efficiency anterior and posterior ocular delivery in a non-human primate model (NHP). A single dose of about 7mg JV-MD2 (omega-3 DHA) via the NIODP reached the retina at Cmax of 111µg/g and the cornea at Cmax of 66µg/g. NIODP also delivered JV-DE1, an anti-inflammatory agent in development for dry eye diseases, as efficiently as eye drops did to anterior segments of NHP. The topical NIODP seems to transport drug candidates through the cornea pathway to the anterior and via the conjunctiva/sclera pathway to the posterior segments of the eye. The novel NIODP method has the potential to reshape the landscape of ocular drug delivery, especially for oily eye drops and retinal delivery, where the success of treatment lies in the ocular tolerability and bioavailability of drugs in the target tissue.

This paper is referred to a top frontline research in life science, showing that in spite of the large variation of the physiological architecture and behavioral forms of the living systems, the fundamental structure of their informational system is basically the same, allowing the body growth/development by micro to macro-structuration processes, maintaining the same informational configuration and functions like the basic unit of life – the eukaryotic cell. Starting and based on the determination of the special/specific info-operability in living structures and the role of information in structuration and their functionality, there are discussed the informational functions of the eukaryotic/prokaryotic cells, the simplest units of life and is elaborated and presented the Informational Model of the Living Structures, showing that these structures operate on the basis of two main informational systems: one of them defined as the Programmed Informational System, composed by three components, assuring respectively the info-generation, maintenance and the proliferation/reproduction, and another one defined as the Operative Informational System, necessary for the continuous communication with the environment for adaptation, consisting in four main components referred to memory, decision, sentience and info-connection/info-selection. The revealed properties are compared with the Informational System of the Human Body, as a prototype of a living system on the top of the evolutionary scale, showing/demonstrating the compatibility of structuration and functions on the entire scale, from prokaryotic/eukaryotic unit cells to multicellular organisms – plants, animals and human, by means of a continuous adaptation process, which always follows the same line of micro to macro-structuration process based on the same Info-organization and functionality. These models are new and revolutionary in the information and life sciences

Compressive sensing (CS) is a technique that allows a signal vector to be reconstructed with a number of linear measurements far fewer than its size. In this study, optical hybrid cryptography with simultaneous compressive sensing based on orthogonal matching pursuit (OMP) is proposed as an alternative solution to the two important problems in communications, namely, effective / efficient / signal processing and secure encryption/decrypton. The whole system is able to both compress and encrypt data with attack immunity.

Chromothripsis is a mutational mechanism leading to complex and relatively clustered chromosomal rearrangements resulting in diverse phenotypic outcomes depending on the involved genomic landscapes. It may occur both in the germ and the somatic cells resulting in congenital and developmental disorders and cancer, respectively. Asymptomatic individuals may be carriers of chromotriptic rearrangements and experience recurrent reproductive failures when two or more chromosomes are involved. Several mechanisms are postulated to underly chromothripsis. The most attractive hypothesis involves chromosome pulverization in micronuclei followed by incorrect reassembly of fragments through DNA repair to explain the clustered nature of the observed complex rearrangements. Moreover, exogenous or endogenous DNA damage induction and dicentric bridge formation may be involved. Chromosome instability is commonly observed in the cells of patients with DNA-repair disorders, such as ataxia telangiectasia, Nijmegen breakage syndrome and Bloom syndrome. In addition, germline variations of TP53 have been associated with chromothripsis in Sonic-Hedgehog medulloblastoma and acute myeloid leukemia. In the present review, we focus on the underlying mechanisms of chromothripsis and the involvement of defective DNA-repair genes resulting in chromosome instability and chromothripsis-like rearrangements.

Although congenital sensorineural hearing loss (SHL) in the bilateral cochleae mainly results from genetic abnormalities, chronic SHL progressing in later life is often influenced by systemic immune disturbances, including autoimmunity, chronic inflammation, and immunosenescence. We have investigated the relationship between the inner ear and systemic immunity and reviewed the possibilities to prevent SHL, including autoimmune SHL and age-related SHL. We also demonstrated two lymphocyte populations, interleukin 1 receptor type II (IL-1R2)-positive T cells (T1R2) and naturally occurring regulatory T cells (nTregs) in CD4⁺ T cells, which increase with aging, suppress host immune function and promote organ degeneration. Alterations in systemic immunity by fewer microbial antigen challenges in the living environment, elimination of immune suppressive lymphocytes, or immune rejuvenation with a reconstituted thymus may contribute not only to renew the cochlear function in SHL, but also to extend the healthy life of functional organs in a vigorous and youthful body, one of humanity’s greatest dreams.

The introduction of any new disruptive technology in a traditionally well-established industry, such as the road construction industry, is usually associated with considerable resistance. This is especially relevant when the new technology is based on the use of granular materials traditionally considered to be of an unacceptable quality in combination with relatively new concepts such as New-age (Nano) Modified Emulsions (NME). In such cases, the fact that the material design methods are based on fundamental scientific principles and have been proven in laboratories and through Accelerated Pavement Testing (APT), may be of little influence. However, the general acceptance of new disruptive technologies, e.g. telecommunications and Information Technologies (IT), have been based on the considerable advantages it presented. The same principles are applicable to the general acceptance and use of NME stabilisation/enhancement of materials in the road construction industry. This article is aimed at the practical demonstration of the advantages of the use of nanotechnologies in the construction of the highest order roads (i.e. inter-city multi-lane highways) to lower order access roads (i.e. Low-Volume-Roads (LVR) and even local accesses to farms and in villages/townships). The implementation of NME technologies is directly associated with ease of use, time and cost savings and the addressing and reduction of risks.

We consider the financial planning problem of a retiree wishing to enter a retirement village at a future uncertain date. The date of entry is determined by the retiree's utility and bequest maximisation problem within the context of uncertain future health states. In addition, the retiree must choose optimal consumption, investment, bequest and purchase of insurance products prior to her full annuitisation on entry to the retirement village. A hyperbolic absolute risk-aversion (HARA) utility function is used to allow necessary consumption for basic living and medical costs. The retirement village will typically require an initial deposit upon entry. This threshold wealth requirement leads to exercising the replication of an American put option at the uncertain stopping time. From our numerical results, active insurance and annuity markets are shown to be a critical aspect in retirement planning.

Populations with essential hypertension have a high risk of nonalcoholic steatohepatitis (NASH). In this study, we investigated the mechanism that underlies the progression of hypertension-associated NASH by comparing differences in the development of high fat and cholesterol (HFC) diet-induced NASH among three strains of rats, i.e., two hypertensive strains comprising spontaneously hypertensive rats and the stroke-prone spontaneously hypertensive 5/Dmcr, and the original Wistar Kyoto rats as the normotensive control. We investigated histopathological changes and molecular signals related to inflammation in the liver after feeding with the HFC diet for 8 weeks. The diet induced severe lobular inflammation and fibrosis in the livers of the hypertensive rats, whereas it only caused mild steatohepatitis in the normotensive rats. Increased activation of proinflammatory signaling (transforming growth factor-β1/mitogen-activated protein kinases pathway) was observed in the hypertensive strains fed with the HFC diet. In addition, the HFC diet suppressed the nuclear factor erythroid 2-related factor 2 pathway in the hypertensive rats and led to lower increases in the hepatic expression of heme oxygenase-1, which has anti-oxidative and anti-inflammatory activities. In conclusion, these signaling pathways might play crucial roles in the development of hypertension-associated NASH.

To investigate factors associated with the success of switching to faricimab for type 1 macular neovascularization (MNV) refractory to intravitreal aflibercept (IVA). This retrospective cohort study included patients with type 1 MNV who were switched to faricimab because they were refractory to IVA at two centers. The main outcome was an extension of the treatment interval after 6 months, and factors related to the success or failure of the extension and visual and anatomical outcomes were assessed. The analysis included 43 eyes of 43 patients. Extended dosing intervals of more than 2 weeks were identified in 14 eyes (32.6%). A short dosing interval before the switch, the absence of polypoidal lesions, and a thin central choroidal thickness before the switch were identified as factors involved in successful extension. For patients with refractory type 1 MNV, switching to faricimab is a safe and potential option to extend from existing dosing intervals.

Objectives: We aimed to clarify the endoscopic and clinicopathological features of raspberry-shaped gastric lesions (RSGLs) and to establish an endoscopic diagnostic algorithm for RSGLs. Methods: We collected RSGLs from an endoscopic database at our hospital between May 2009 and August 2021. All RSGLs were histopathologically classified and compared based on their endoscopic and clinicopathological characteristics. Results: Sixty-five RSGLs in 54 patients were classified into five histopathological types: gastric adenocarcinoma of foveolar type (GA-FV, n = 43), gastric adenocarcinoma of fundic-gland type (GA-FG, n = 2), gastric adenocarcinoma of fundic-gland mucosa type (GA-FGM, n = 4), hyperplastic polyp (HP, n = 12), and proton pump inhibitor-related lesion (PPI-L, n = 4). All RSGLs exhibited polygonal or curved marginal crypt epithelium (MCE). GA-FV lesions had homogenously reddish (95%) and irregular microvascular (MV) pattern (91%). GA-FG lesions were heterogeneously reddish with a submucosal tumor shape (100%) and had a regular MV pattern (50%). GA-FGM lesions were homogenously reddish (75%) and occasionally had a submucosal tumor shape (50%) with an irregular MV pattern (75%). HP and PPI-L were homogeneously reddish (93%), with linear or dotted MCE (81%) and a regular MV pattern (100%). Conclusion: Our diagnostic algorithm for RSGLs constructed using endoscopic features might be useful for the endoscopic differential diagnosis of RSGLs.